The long term objective of this research is to determine whether lysophospholipids have therapeutic value in treatment of conditions associated with herpes simplex virus-1 (HSV-1) and possibly other envelope viruses including human immunodeficiency virus (HIV). Envisioned potential applications range from systemic treatment of viremia, to topical treatment of lesions to "in vitro" inactivation of envelope viruses in blood derived fractions used to treat hemophilia and other disorders. The specific aims of this project were developed on the basis of a preliminary observation that lysophosphatidyl choline (LPC) a normal constituent of human plasma and lysophosphatidyl ethanolamine, derived from egg, inactivate HSV-1 at concentrations which do not injure vero cells used as the virus assay system. The specific aims are: 1. To measure the degree of HSV-1 inactivation as a function of virus concentration and LPC concentration for LPCs containing fatty acids of varying chain length with and without a double bond. 2. To determine for each antiviral LPC the ratio (minimum 100% virucidal concentration/vero cell threshold cytotoxic concentration) as a preliminary indication of which LPCs could be used as viral inactivators in living cell systems. 3. To determine whether LPCs are hydrolyzed during incubation with the virus thereby releasing fatty acid which inactivates the virus or whether LPCs act directly. 4. To determine whether LPC inactivation of HSV-1 in reversible. 5. To determine whether LPCs disrupt the HSV-I envelope. Experimental procedures will be as follows: Aim 1 and 2; various concentrations of HSV-I and saturated and unsaturated LPCs will be incubated at room temperature for 30 min. and analyzed for infectivity with a vero cell monolayer plaque assay. Aim 3; Virus-LPC samples will be analyzed for released fatty acid and residual LPC as a function of incubation time. Extent of virus inactivation by released fatty acid concentrations and LPC will be measured to estimate the free fatty acid contribution. Aim 4; High tittered virus, inactivated by LPC will be serially diluted to reduce the LPC concentration to a non inhibitory level and assayed in the vero cell plaque system for reappearance of infectivity. Inactivated virus will be diluted with liposomes prepared from phospholipids of viral stock and tested for reappearance of infectivity. Aim 5; sucrose and ficol density gradient purified HSV-I will be treated with LPC and re-analyzed by density gradient centrifugation. Fractions will be examined by electron microscopy to determine whether LPC disrupts the viral envelope and the nucleocapsid.